China-based drug maker TOT Biopharm is developing TAB008 as a biosimilar of the reference bevacizumab, Avastin. TOT has recently indicated that it is in the midst of a phase 3 clinical trial of the biosimilar, and last month, results of a phase 1 study of the biosimilar were published in Frontiers in Pharmacology.
China-based drug maker TOT Biopharm is developing TAB008 as a biosimilar of the reference bevacizumab, Avastin. TOT has recently indicated that it is in the midst of a phase 3 clinical trial of the biosimilar, and the company also raised $102 million last month in series B financing that will, in part, help finance the continued development of the product.
Last month, results of a phase 1 study of the biosimilar were published in Frontiers in Pharmacology after having previously been reported in abstract form at the American Society of Clinical Oncology meeting in 2018, and the study’s authors write that, as well as showing pharmacokinetic (PK) similarity to reference bevacizumab, the biosimilar was safe and well tolerated.
In the randomized, double-blind, parallel controlled study, 100 healthy male volunteers were randomized to receive a single 1-mg/kg dose intravenous dose of either the biosimilar (n = 49, as 1 volunteer experienced an adverse event [AE] not related to the study drug) or the reference bevacizumab (n = 50).
The primary PK parameters were maximum observed concentration (Cmax), the area under the plasma drug concentration—time curve up to time t (AUC0-t), and the area under the plasma drug concentration—time curve to infinite time (AUC0-∞).
The mean concentration profiles between the biosimilar and the reference were similar; the treatment group ratios of the least squares geometric means for the 3 primary PK parameters were fully contained within the prespecified bioequivalence margin of 80.00% to 125.00% (90% CI, 103.66%-118.33% for Cmax; 94.32%-111.72% for AUC0-t; 94.69%-112.23% for AUC0-∞).
Treatment-emergent AEs (TEAEs) were reported in 49.0% of volunteers in the biosimilar group and 44.0% of volunteers in the reference group. TEAEs considered related to bevacizumab were reported in 38.8% of the biosimilar group and 38.0% of the reference group. One volunteer in the biosimilar group and 3 in the reference group experienced grade 3 TEAEs. No TEAEs led to discontinuation.
The most frequently reported AE in both arms was hypertriglyceridemia, and clinically significant hypertension was also observed in both groups. Electrocardiograms and physical examination did not show clinically relevant abnormalities in either group, however.
In terms of immunogenicity, 1 volunteer in the biosimilar group and 1 in the reference group developed new antibodies to bevacizumab. The antidrug antibodies were nonneutralizing.
According to the authors, this study demonstrates that the proposed biosimilar has similar PK to the reference, was safe, and is well tolerated.
Wang J, Qui L, Liu L, et al. A phase 1, randomized, single-dose study evaluating the biosimilarity of TAB008 to bevacizumab in healthy volunteers. Front Pharmacol. 2019;10:905. doi: 10.3389/fphar.2019.00905.